Red blood cell membrane defects NGS panel

The Sanquin Red Blood Cell Membrane NGS Panel ( test code X007-X012) includes 10 genes and regions of interest.

The inherited hemolytic anemias due to an erythrocyte membrane defect include hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and hereditary stomatocytosis /xerocytosis. The clinical presentation is divers, underlying mutations are heterogenetic and often family specific. A damaged cytoskeleton may lead to membrane loss, to decreased red cell deformability and premature removal of the erythrocytes from the circulation. Hereditary spherocytosis is the most common congenital hemolytic anemia among Caucasians with an estimated prevalence ranging from 1:2,000 to 1:4,000. Often dominant due to family specific mutations in ANK, SPTB or SLC4A1. In one third of the cases spherocytosis appeared autosomal recessive or de novo. The clinical manifestations can vary from mild to severe hemolytic anemia requiring regular transfusions, variable jaundice, splenomegaly and cholelithiasis. Hereditary elliptocytosis/ovalocytosis is an autosomal dominant defect and usually asymptomatic.  Approximately ten percent of the cases may have moderate to severe anemia including the cases with the severe variant of pyropoikilocytosis. This severe form is often caused by inheritance of two abnormal spectrin alleles. Elliptocytosis/ovalocytosis is more common in patients originated from West Africa with the prevalence of 2%. Hereditary stomatocytosis/xerocytosis is an autosomal dominant disorder characterized by the presence  of stomatocytes in blood smear associated with moderate to severe anemia. Splenectomy is very beneficial in the treatment of hereditary spherocytosis and elliptocytosis but contraindicated in hereditary stomatocytosis, because it may increase the risk of thromboembolic complications.